Table of Contents

HK J Paediatr (New Series)
Vol 24. No. 1, 2019

HK J Paediatr (New Series) 2019;24:43-47

Case Report

The First Case of Cobalamin F Disorder in China: Report and Literature Review
中國首例鈷胺素(維生素B12)F障礙:報告和文獻綜述

F Tong, RL Yang, R Chen, ZY Zhao


Abstract

Objectives: To investigate the phenotype, genotype and prognosis of cblF disorder (CblF). Methodology: Data including newborn screening and clinical features, LMBRD1 mutations, treatment and prognosis of the first CblF case in China and 17 reported CblF cases were collected and analysed. Results: This case was picked up by newborn screening (NBS) due to elevated blood propionylcarnitine (C3) (5.50 μmol/L), propionylcarnitine / acetylcarnitine (C3/C2) ratio (0.47), propionylcarnitine / free carnitine C3/C0 ratio (0.25) and decreased methionine (Met) (5.27 μmol/L) identified by tandem mass spectrometry (MS-MS), then decreased serum Vitamin B12 (cobalamin; Vit B12) (116 pmol/L), elevated homocysteine (tHCY) (82.9 μmol/L), macrocytic anaemia and atrial septal defect, and patent ductus arteriosus were confirmed. This is similar to what has been reported in the literature. Besides, two novel truncated LMBRD1 mutations of p.R277* and p.C29* were confirmed. The data of all the 18 cases show that the common clinical features are macrocytic anaemia, failure to thrive, developmental delay, congenital heart disease, and small for gestational age. Similar biochemical characters were identified in all 3 cases from NBS, and a total of 35 LMBRD1 mutations in 10 different sites including frame-shift mutations (30/35), splice site mutations (2/35), nonsense mutations (2/35), and large fragment deletions (1/35) were observed, among which c.1056delG mutation was reported the most frequently (24/35). After Vit B12 injection and supportive treatment, all of the biochemical abnormalities and most of the clinical presentations have been significantly improved within 3 months in all cases. Conclusion: The biochemical characters of CblF are similar to the combined methylmalonic acid (MMA), except for decreased serum Vit B12, which should be distinguished from Vit B12 deficiency. Typical phenotype includes macrocytic anaemia, growth and development problems, and congenital malformations, all of which are nonspecific. The c.1056delG mutation is the common mutation. The concentrations of C3, C3/C2, C3/C0 and Met by MS-MS and the target genetic panel of MMA should be chosen for suspected MMA cases. CblF is a treatable disease, and injection of Vit B12 is effective, but the appropriate dosage remains unclear.

目的:探討鈷胺素F障礙(CblF)表型、基因型和預後。方法:資料包括中國首例CblF 障礙的新生兒篩查和臨床特徵,LMBRD1突變,在治療和預後和17 CblF病例收集和分析報告。結果:本例由新生兒篩查(NBS)發現,因血串聯質譜(MS-MS)檢查出丙肉鹼(C3)(5.50 μmol / L),丙肉鹼/乙肉鹼(C3/C2)比(0.47),丙肉鹼/肉鹼自由基C3/C0比(0.25)和蛋氨酸(Met)減低(5.27 μmol / L),血清維生素B12(氰鈷胺素;維生素B12)減少(116 pmol / L),同型半胱氨酸升高(血漿總高半胱氨酸水準)(82.9 μmol / L),並證實合併大細胞性貧血,心房間隔缺損,動脈導管未閉。與文獻已報導相類似。此外,兩個新的 LMBRD1基因的 p.R277 *和p.C29 *截斷突變獲證實。所有18例的資料表明,常見的臨床特徵是大細胞性貧血、生長遲滯、發育遲緩、先天性心臟病和小胎齡。NBS的3個病例均有相似的生化特徵,在10個不同的位點共觀察到35個 LMBRD1突變,包括框移突變(0/35)、剪切位點突變(2/35)、無意義突變(2/35)和大片段缺失(1/35),其中 c.1056delG 突變是最常報導(24/35)。維生素B12注射和支持治療3個月後,所有的病例的生化異常和大多數臨床表現都顯著改善。結論:CblF生化特點與甲基丙二酸(MMA)類似,除了降低血清維生素B 12之外,應區別於維生素B12缺乏症。典型的表型包括大細胞性貧血、生長和發育問題和先天畸形,這些都是非特異性的。 c.1056delG 突變是常見的突變。疑似MMA病例可選擇MS-MS檢查C3,C3 / C2,C3 / C0,Met濃度和MMA基因檢測。CblF是一種可以治癒的疾病和注射維生素B 12是有效的,但合適的劑量仍有待確定。

Keyword : Cobalamin; Genotype; Phenotype; Prognosis; Treatment

關鍵詞:鈷胺素、基因型、表型、預後、治療

 
 

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